FuzDrop on AlphaFold: visualizing the sequence-dependent propensity of liquid-liquid phase separation and aggregation of proteins.
FuzDrop on AlphaFold: visualizing the sequence-dependent propensity of liquid-liquid phase separation and aggregation of proteins.
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DOI：
10.1093/nar/gkac386
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发表时间：
2022-07-05
影响因子：
14.9
通讯作者：
Fuxreiter, Monika
中科院分区：
文献类型：
--
作者：
Hatos, Andras;Tosatto, Silvio C. E.;Vendruscolo, Michele;Fuxreiter, Monika
许多蛋白质在无膜细胞器中发挥其功能，形成类似液体的凝聚态，也称为液滴态。 FuzDrop 方法预测蛋白质自发液-液相分离的概率，并提供基于序列的评分来识别促进该过程的区域。此外，FuzDrop 方法估计蛋白质转化为淀粉样蛋白状态的倾向，并识别聚集热点，这可以驱动液体状液滴状态的不可逆成熟。这些预测还可以识别可诱导淀粉样蛋白聚集体形成的突变，包括与人类疾病有关的突变。为了便于解释预测，可以在 AlphaFold 生成的蛋白质结构上可视化促进液滴和聚集的区域。因此，FuzDrop 服务器 (https://fuzdrop.bio.unipd.it) 提供了对蛋白质在凝聚状态下的复杂行为的见解，并有助于理解蛋白质的功能关系。 FuzDrop 服务器 (https://fuzdrop.bio.unipd.it) 提供基于序列的预测：(i) 发生自发液-液相分离的概率和 (ii) 液滴内聚集的可能性。
Many proteins perform their functions within membraneless organelles, where they form a liquid-like condensed state, also known as droplet state. The FuzDrop method predicts the probability of spontaneous liquid–liquid phase separation of proteins and provides a sequence-based score to identify the regions that promote this process. Furthermore, the FuzDrop method estimates the propensity of conversion of proteins to the amyloid state, and identifies aggregation hot-spots, which can drive the irreversible maturation of the liquid-like droplet state. These predictions can also identify mutations that can induce formation of amyloid aggregates, including those implicated in human diseases. To facilitate the interpretation of the predictions, the droplet-promoting and aggregation-promoting regions can be visualized on protein structures generated by AlphaFold. The FuzDrop server (https://fuzdrop.bio.unipd.it) thus offers insights into the complex behavior of proteins in their condensed states and facilitates the understanding of the functional relationships of proteins. The FuzDrop server (https://fuzdrop.bio.unipd.it) provides sequence-based predictions of: (i) the probability to undergo spontaneous liquid–liquid phase separation and (ii) the likelihood to aggregate within the liquid droplets.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1021/acs.jpcb.0c11068
发表时间：
2021-03-18
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Freiberger MI;Wolynes PG;Ferreiro DU;Fuxreiter M
通讯作者：
Fuxreiter M
影响因子：
64.8
作者：
Larson AG;Elnatan D;Keenen MM;Trnka MJ;Johnston JB;Burlingame AL;Agard DA;Redding S;Narlikar GJ
通讯作者：
Narlikar GJ
影响因子：
64.5
作者：
Boija A;Klein IA;Sabari BR;Dall'Agnese A;Coffey EL;Zamudio AV;Li CH;Shrinivas K;Manteiga JC;Hannett NM;Abraham BJ;Afeyan LK;Guo YE;Rimel JK;Fant CB;Schuijers J;Lee TI;Taatjes DJ;Young RA
通讯作者：
Young RA
影响因子：
21.3
作者：
Fuxreiter, Monika;Vendruscolo, Michele
通讯作者：
Vendruscolo, Michele